In this reapplication I propose a comprehensive and rigorous program for my development as an independent clinical investigator. The components of my career development program are formal courseworkj intense mentoring and performing a pilot study on the interrelationships between bacteremia, cytokine expression and graft versus host disease (GVHD) in recipients of bone marrow tranplantation (BMT). My career development will utilize the Tufts-New England Medical Center (T-NEMC) General Clinical Research Center (GCRC) and the Nffl-funded K30 Clinical Care Research Graduate Program of T-NEMC. Formal coursework will include biostatistics, clinical trial design, epidemiology, evidence-based medicine, predictive modeling and meta-ahalysis, and the ethics of clinical investigation. A structured mentored research program which will involve all aspects of my efforts, will be directed by Dr. David Snydman, an internationally recognized authority on transplantation-related infections, Dr. Patricia Hibberd, the Program Director of the T-NEMC GCRC and Dr. Megan Sykes, a pioneer and expert in BMT immunology. Ultimate and immediate career goals are,respectively, to direct an effort focusing on the prevention of infection and its consequences in immunocompromised persons, and to study bacteremia in recipients of bone marrow transplantation (BMT). Bacteremia is the most common infectious complication of BMT. GVHD, one of the major morbidities after BMT, is triggered by cytokine expression occurring at the time of the conditioning regimen. We hypothesize that bacteremia has a direct effect on the development or worsening of GVHD through a similar cytokine-mediated mechanism. The proposed research project consists of the following aims: Specific Aim 1: a prospective cohort study design will be used to determine if bacteremia is a predictor of acute GVHD. Specific Aim 2: to explore the relationships between cytokine expression during bacteremia and the development of GVHD. Specific Aim 3: to determine if cytokine gene polymorphisms, as detected by PCR-SSNP technology, are predictive of the development of acute GVHD after bacteremia. Specific Aim 4: to plan and submit an R01 application in the next step in my long-term career path of the study of infection of immunocompromised individuals. The K23 Award will enable my development as an independent clinical investigator by allowing me to (1) receive formal didactic training, (2) develop expertise in the planning, execution and sophisticated analysis of different types of clinical studies, (3) develop expertise and contribute to the knowledge base of infections in immunocompromised persons thereby providing the basis for future investigations and (4) write manuscripts and applications for future independent funding.